Serotype-specific mortality from invasive Streptococcus pneumoniae disease revisited

BACKGROUND: Invasive infection with Streptococcus pneumoniae (pneumococci) causes significant morbidity and mortality. Case series and experimental data have shown that the capsular serotype is involved in the pathogenesis and a determinant of disease outcome. METHODS: Retrospective review of 464 cases of invasive disease among adults diagnosed between 1990 and 2001. Multivariate Cox proportional hazard analysis. RESULTS: After adjustment for other markers of disease severity, we found that infection with serotype 3 was associated with an increased relative risk (RR) of death of 2.54 (95% confidence interval (CI): 1.22–5.27), whereas infection with serotype 1 was associated with a decreased risk of death (RR 0.23 (95% CI, 0.06–0.97)). Additionally, older age, relative leucopenia and relative hypothermia were independent predictors of mortality. CONCLUSION: Our study shows that capsular serotypes independently influenced the outcome from invasive pneumococcal disease. The limitations of the current polysaccharide pneumococcal vaccine warrant the development of alternative vaccines. We suggest that the virulence of pneumococcal serotypes should be considered in the design of novel vaccines

Invasive Pneumococcal Infections in Denmark from 1995 to 1999: Epidemiology, Serotypes, and Resistance

Danish nationwide surveillance data on invasive pneumococcal disease from the 5-year period from 1995 to 1999, including 5,452 isolates, are presented and described. Annual overall incidence rates, serotype distribution, and antimicrobial susceptibility patterns of the isolates were monitored. Major changes in the total annual incidence rate from 27/100,000 in 1996 to 17/100,000 in 1999 and a significant change in the proportion of invasive isolates belonging to types 1 and 12F were observed. The serotype coverage rate by the 23-valent polysaccharide vaccine among the elderly was 92.9%, and the serotype coverage rate by the 7-, 9-, and 11-valent pneumococcal conjugate vaccines among children less than 2 years old were 71.7, 75.2, and 81.4%, respectively. Invasive isolates with reduced susceptibility to penicillin or erythromycin increased from 1995 to 1999, with a high proportion of the penicillin-nonsusceptible invasive isolates originating from people 60 years old or older (57.0%). These observations underline the importance of adequate surveillance systems of invasive pneumococcal disease to introduce and maintain national vaccine strategies and adequate antibiotic policy

Reemergence of emm1 and a Changed Superantigen Profile for Group A Streptococci Causing Invasive Infections: Results from a Nationwide Study

Between 1999 and 2002, 496 invasive group A streptococcal (GAS) isolates from clinical microbiological departments in Denmark and subsequently 487 (98%) questionnaires from the clinicians treating the patients were received as part of a national surveillance. emm types and streptococcal superantigen (SAg) genes were determined. The incidence of invasive GAS infections was on average 2.3 per 100,000 per year. Bacteremia with no focal symptoms (27%) was together with erysipelas (20%) the most prevalent clinical diagnoses. Streptococcal toxic shock syndrome occurred in 10% of patients, of which 56% died. The overall case fatality rate within 30 days was 23%. In total, 47 different emm types were identified, of which emm1, emm3, emm4, emm12, emm28, and emm89 were identified in 72% of the 493 available isolates. During the 4-year period the presence of emm1 increased from 16% in 1999 to 40% in 2002. Concurrently, the presence of emm3 decreased from 23% in 1999 to 2% in 2002. The emm1 isolates predominantly carried speA, although the frequency decreased from 94% in 1999 to 71% in 2002, whereas the emm1-specific prevalence of speC increased from 25 to 53%. In a historical perspective, this could be interpreted as a reemergence of emm1 and could indicate a possible introduction of a new emm1 subclone. However, this reemergence did not result in any significant changes in the clinical manifestations during the study period. Our results show the complexity of invasive GAS infections, with time-dependent variations in the incidence and distribution of emm and SAg genes, which emphasizes the need for continuous epidemiological and molecular investigations

2000. Recurrence of pneumonia in relation to the antibody response after pneumococcal vaccination in middle-aged and elderly

We have recently studied the efficacy of pneumococcal vaccine in preventing pneumonia recurrences after hospital treatment for community-acquired pneumonia in non-immunocompromised patients aged 50 -85 y. Among these patients, we have now compared the antibody response to the pneumococcal vaccine between patients who developed pneumonia (n =50) and patients without pneumonia recurrences (n= 100), during a mean follow-up period of 32 months after vaccination. The antibody levels of 5 pneumococcal serotypes were measured before, and 4 weeks, 1 y and 3 y after vaccination. A lower risk of pneumonia recurrences was seen in patients with antibody fold increases (FIs) \ 4 from pre-vaccination to post-vaccination compared with patients with lower FIs (p =0.02). The results suggest that in this patient category, the antibody response to pneumococcal vaccination is of importance for the risk of pneumonia recurrence

Comparison of Two Urinary Antigen Tests for Establishment of Pneumococcal Etiology of Adult Community-Acquired Pneumonia

The Binax NOW immunochromatographic test (ICT) detecting the pneumococcal C polysaccharide and a serotype-specific latex agglutination (LA) test detecting 23 pneumococcal capsular antigens were evaluated for establishing pneumococcal etiology in community-acquired pneumonia (CAP) by use of nonconcentrated urine. ICT was considered to be strongly positive for result lines at least as intense as the control line and weakly positive for less intense result lines. When 215 adult CAP patients were tested, strong ICT, weak ICT, and LA positivity were found in 28, 24, and 16 patients, respectively; of these patients, 13 (46%), 6 (25%), and 13 (81%), respectively, had pneumococcal bacteremia and 27 (96%), 17 (71%), and 15 (94%), respectively, had Streptococcus pneumoniae isolated from blood, sputum, and/or nasopharynx. Among 108 controls tested, 2 (1.9%) were weakly ICT positive. When weak positivity was considered negative, the sensitivity of ICT decreased from 79% (19 of 24) to 54% (13 of 24), while the specificity increased from 83% (158 of 191) to 92% (176 of 191); no controls were false positive. The sensitivity and specificity of LA were 54% (13 of 24) and 98% (188 of 191), respectively. Eight of nine LA serotypes corresponded to culture serotypes. In conclusion, using nonconcentrated urine and dividing ICT-positive results into strongly and weakly positive results is a suitable way of performing ICT. While weak ICT positivity should be interpreted with caution, strong ICT positivity and LA positivity should be considered supportive of pneumococcal etiology in adult CAP. As such, these assays might have implications for antibiotic use in CAP. LA has promising potential for pneumococcal serotyping, although further evaluation is required